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Risk Assessment Tools
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Tim Sandle
The University of Manchester
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Tim Sandle
Over the past decade environmental monitoring has become more sophisticated in
moving from random sampling, using an imaginary grid over the room and testing in
each grid, to the current focus on risk assessment and the use of risk assessment tools
to determine the most appropriate methods for environmental monitoring.
Risk based approaches include FMEA (Failure Mode and Effects Analysis); FTA
(Fault Tree Analysis) and HACCP (Hazard Analysis Critical Control Points), all of
which employ a scoring approach1. At present, no definitive method exists and the
various approaches differ in their process and the degree of complexity involved.
However, the two most commonly used appear to be HACCP (which originated in the
food industry) and FMEA (which was developed for the engineering industry) (Whyte
and Eaton, 2004a).
These risk assessment approaches are not only concerned with selecting
environmental monitoring locations. They integrate the environmental monitoring
system with a complete review of operations within the clean room to ensure those
facilities, operations and practices are also satisfactory. The approaches recognise a
1
Other approaches include FMECA (Failure Mode Effect and Criticality Analysis); HAZOP (Hazard
and Operational Studies); QMRA (Quantitative Microbiological Risk Assessment); MPRM (Modular
Process Risk Model); SRA (System Risk Analysis); Method for Limitation of Risks and Risk Profiling.
risk, rate the level of the risk and then set out a plan to minimise, control and monitor
the risk. The monitoring of the risk will help to determine the frequency, locations for
and level of environmental monitoring (for example, refer to an article by Sandle
[2003a], for a more detailed example).
Each of these ‘seven key points’ is a vital step in developing the risk assessment. The
seven points include:
2. Assess the importance of these sources and if they are / are not hazards
that need to be controlled. Examples include:
3. Identify the methods that can be used to control these hazards. For
example:
Before implementing HACCP it is important to train all staff involved in the process
and to use a multi-disciplinary team. For example, this may be made up of personnel
from production, engineering, QC/QA, validation and so on.
Example 3: FMEA
FMEA schemes vary in their approach, scoring and categorisation. All approaches
share in common a numerical approach. The example here, based on a sterility testing
isolator, was to assign a score (from 1 to 5) to each of the following categories:
i) Severity
ii) Occurrence
iii) Detection
Where:
i) Severity is the consequence of a failure
ii) Occurrence is the likelihood of the failure happening (based on past experience)
iii) Detect is based on the monitoring systems in place and on how likely a failure can
be detected.
By asking a series of questions each main part of the clean room or isolator system
can be broken down into key parts. Such questions included:
i) What is the function of the equipment? How are its performance requirements?
ii) How can it fail to fulfil these functions?
iii) What can cause each failure?
iv) What happens when each failure occurs?
v) How much does each failure matter? What are its consequences?
vi) What can be done to predict or prevent each failure?
vii) What should be done if a suitable proactive task cannot be found?
The scoring is 1 (very good) to 5 (very bad). Therefore, a likelihood of high severity
would be rated 5; high occurrence rated 5; but a good detection system would be rated
1.
Using these criteria a final FMEA score is produced:
x
125
From: severity score x occurrence score x detect score
Depending upon the score produced it can be decided whether further action is
needed. There is no published guidance on what the score that dictates some form of
action should be. A suggested score is 27 for the cut-off value where action was
required. This was based on 27 being the score derived when the mid-score is applied
to all three categories (i.e. the numerical value '3' from severity (3) x occurrence (3) x
detect (3)) and the supposition that if the mid-rating (or a higher number) was scored
for all three categories then as a minimum the system should be examined in greater
detail.
An example of one area of an isolator operation (the risks associated with the room in
which the isolator is housed) is examined below.
Description of critical area: The isolator is situated in an unclassified room. There is
not requirement to place a sterility testing isolator in a classified room.
FMEA schematic:
FMEA score: 3 x 1 x 1 = 3
Analysis: There is no problem considered from the room environment. Entry to the
room is controlled; the sanitisation cycle has been challenged with a level of micro-
organisms far greater than would ever be found in the environment (spores of
Geobacillus stearothermophilus); all items entering the isolator are sanitised (using a
chlorine dioxide based sporicidal disinfectant) and the isolator itself is an effective
positive pressure barrier to the outside (at >15 pascals).
Numerical approaches
A third component of the risk assessment approach is to evaluate the risk once an
activity has taken place. By using a largely numerically driven set of tools then
repeatability and reproducibility can be ensured. Examples of individual out of limits
results and data sets relating to an operation are examined below, using examples
from an aseptic filling process. Following this an example of an overall assessment of
different processes over time are explored. Numerical approaches are useful in
applying a level of consistency between one decision and another.
Conclusion
This paper has outlined some possible tools for such a risk assessment approach.
However, each suite of clean rooms or isolator will be subtly different. The
microbiologist needs to consider each aspect of the environment and decide what
level of monitoring best suits their system, and then to justify the techniques used and
the locations selected.
The approach adopted should be detailed in a written rationale and approved by senior
management. After this a rigorous and defensible system will be in place to satisfy
regulatory expectations, and to aid the user in risk assessing problematic
environmental monitoring situations and results.
Sandle, T. (2003a): ‘The use of a risk assessment in the pharmaceutical industry – the
application of FMEA to a sterility testing isolator: a case study’, European Journal of
Parenteral and Pharmaceutical Sciences, 2003; 8(2): 43-49